Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Signaling by brain-derived neurotrophic factor (BDNF) via the TrkB receptor, or by neurotrophin-3 (NT3) through the TrkC receptor support distinct populations of sensory neurons. The intracellular signaling pathways activated by Trk (tyrosine kinase) receptors, which in vivo promote neuronal survival and target innervation, are not well understood. Using mice with TrkB or TrkC receptors lacking the docking site for Shc adaptors (trkB(shc/shc) and trkC(shc/shc) mice), we show that TrkB and TrkC promote survival of sensory neurons mainly through Shc site-independent pathways, suggesting that these receptors use similar pathways to prevent apoptosis. In contrast, the regulation of target innervation appears different: in trkB(shc/shc) mice neurons lose target innervation, whereas in trkC(shc/shc) mice the surviving TrkC-dependent neurons maintain target innervation and function. Biochemical analysis indicates that phosphorylation at the Shc site positively regulates autophosphorylation of TrkB, but not of TrkC. Our findings show that although TrkB and TrkC signals mediating survival are largely similar, TrkB and TrkC signals required for maintenance of target innervation in vivo are regulated by distinct mechanisms.

Original publication

DOI

10.1101/gad.217902

Type

Journal

Genes Dev

Publication Date

01/03/2002

Volume

16

Pages

633 - 645

Keywords

NASA Discipline Developmental Biology, Non-NASA Center, Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Amino Acid Motifs, Animals, Binding Sites, Brain-Derived Neurotrophic Factor, Cochlea, Conserved Sequence, Ear, Inner, Mice, Mice, Mutant Strains, Neurons, Afferent, Neurotrophin 3, Proteins, Receptor, trkB, Receptor, trkC, Shc Signaling Adaptor Proteins, Signal Transduction, Src Homology 2 Domain-Containing, Transforming Protein 1, Synapses, Vestibule, Labyrinth